Finkielstein Research Group
Our laboratory currently studies the molecular mechanisms of the circadian clock and the cell cycle, with emphasis on how they interface with one another. We explore how these interfaces contribute to the growth of cancer and how an in-depth understanding of them can be used to help develop anti-cancer therapies.
A fundamental feature of all living organisms is the presence of two 24-hour oscillating cyclic systems, the circadian clock and the cell cycle. The circadian clock dictates the timing of many physiological responses and provides the cell with information that can be used to anticipate daily environmental changes. The cell cycle is a series of synchronized events involving the growth, replication, and division of cells. The proper timing of cell division is a major factor contributing to the regulation of normal growth and emerges as a fundamental process in the development of most cancers. Our laboratory investigates some of the basic mechanisms that regulate cell cycle transitions, the contribution of environmental cues to ensure timely progression throughout it, and how both cycles are interlocked at the molecular level.
Lab Members
Name
|
Title
|
---|---|
Bock, Abigail |
Visiting Student |
Henley, Kavon |
Visiting Student |
Lawrence, Brittany |
Visiting Student |
Oker, Helen |
Visiting Student |
Soccio-Mallon, Alexandra |
Visiting Student |
Wisdom, Esther |
Visiting Student |
Zou, Xianlin |
Visiting Student |
2015
Gotoh T, Vila-Caballer M, Liu J, Schiffhauer S, Finkielstein CV. Association of the circadian factor Period 2 to p53 influences p53's function in DNA-damage signaling. Mol Biol Cell. 2015;26:359–372. http://www.ncbi.nlm.nih.gov/pubmed/25411341
Xiao S, Brannon MK, Zhao X, et al. Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism. Structure. 2015;23:1910–1920. http://www.ncbi.nlm.nih.gov/pubmed/26320582
2014
Capelluto DG, Zhao X, Lucas A, et al. Biophysical and molecular-dynamics studies of phosphatidic acid binding by the Dvl-2 DEP domain. Biophys J. 2014;106:1101–1111. http://www.ncbi.nlm.nih.gov/pubmed/24606934
Gotoh T, Vila-Caballer M, Santos CS, Liu J, Yang J, Finkielstein CV. The circadian factor Period 2 modulates p53 stability and transcriptional activity in unstressed cells. Mol Biol Cell. 2014;25:3081–3093. http://www.ncbi.nlm.nih.gov/pubmed/25103245
Lucas AT, Fu X, Liu J, et al. Ligand binding reveals a role for heme in translationally-controlled tumor protein dimerization. PLoS One. 2014;9:e112823. http://www.ncbi.nlm.nih.gov/pubmed/25396429
Xiao S, Zhao X, Finkielstein CV, Capelluto DG. A rapid procedure to isolate isotopically labeled peptides for NMR studies: application to the Disabled-2 sulfatide-binding motif. J Pept Sci. 2014;20:216–222. http://www.ncbi.nlm.nih.gov/pubmed/24470337
2013
Larion S, Caballes FR, Hwang SI, et al. Circadian rhythms in acute intermittent porphyria--a pilot study. Eur J Clin Invest. 2013;43:727–739. http://www.ncbi.nlm.nih.gov/pubmed/23650938
Xiao S, Finkielstein CV, Capelluto DG. The enigmatic role of sulfatides: new insights into cellular functions and mechanisms of protein recognition. Adv Exp Med Biol. 2013;991:27–40. http://www.ncbi.nlm.nih.gov/pubmed/23775689
2012
Xiao S, Charonko JJ, Fu X, et al. Structure, sulfatide binding properties, and inhibition of platelet aggregation by a disabled-2 protein-derived peptide. J Biol Chem. 2012;287:37691–37702. http://www.ncbi.nlm.nih.gov/pubmed/22977233
2011
Alajlouni R, Drahos KE, Finkielstein CV, Capelluto DG. Lipid-mediated membrane binding properties of Disabled-2. Biochim Biophys Acta. 2011;1808:2734–2744. http://www.ncbi.nlm.nih.gov/pubmed/21820403
Cordoba L, Huang YW, Opriessnig T, et al. Three amino acid mutations (F51L, T59A, and S390L) in the capsid protein of the hepatitis E virus collectively contribute to virus attenuation. J Virol. 2011;85:5338–5349. http://www.ncbi.nlm.nih.gov/pubmed/21450834
Gotoh T, Villa LM, Capelluto DG, Finkielstein CV. Regulatory pathways coordinating cell cycle progression in early Xenopus development. Results Probl Cell Differ. 2011;53:171–199. http://www.ncbi.nlm.nih.gov/pubmed/21630146
Howells CC, Baumann WT, Samuels DC, Finkielstein CV. The Bcl-2-associated death promoter (BAD) lowers the threshold at which the Bcl-2-interacting domain death agonist (BID) triggers mitochondria disintegration. J Theor Biol. 2011;271:114–123. http://www.ncbi.nlm.nih.gov/pubmed/21130780
Welsh JD, Charonko JJ, Salmanzadeh A, et al. Disabled-2 modulates homotypic and heterotypic platelet interactions by binding to sulfatides. Br J Haematol. 2011;154:122–133. http://www.ncbi.nlm.nih.gov/pubmed/21539534
2010
Allen WJ, Capelluto DG, Finkielstein CV, Bevan DR. Modeling the relationship between the p53 C-terminal domain and its binding partners using molecular dynamics. J Phys Chem B. 2010;114:13201–13213. http://www.ncbi.nlm.nih.gov/pubmed/20873738
Armenta JM, Perez M, Yang X, et al. Fast proteomic protocol for biomarker fingerprinting in cancerous cells. J Chromatogr A. 2010;1217:2862–2870. http://www.ncbi.nlm.nih.gov/pubmed/20307887
Azurmendi HF, Mitra S, Ayala I, Li L, Finkielstein CV, Capelluto DG. Backbone (1)H, (15)N, and (13)C resonance assignments and secondary structure of the Tollip CUE domain. Mol Cells. 2010;30:581–585. http://www.ncbi.nlm.nih.gov/pubmed/20957454
Dong J, Mury SP, Drahos KE, Moscovitch M, Zia RK, Finkielstein CV. Shorter exposures to harder X-rays trigger early apoptotic events in Xenopus laevis embryos. PLoS One. 2010;5:e8970. http://www.ncbi.nlm.nih.gov/pubmed/20126466
2009
Drahos KE, Welsh JD, Finkielstein CV, Capelluto DG. Sulfatides partition disabled-2 in response to platelet activation. PLoS One. 2009;4:e8007. http://www.ncbi.nlm.nih.gov/pubmed/19956625
2008
Sweede M, Ankem G, Chutvirasakul B, et al. Structural and membrane binding properties of the prickle PET domain. Biochemistry. 2008;47:13524–13536. http://www.ncbi.nlm.nih.gov/pubmed/19053268
Yang J, Kim KD, Lucas A, et al. A novel heme-regulatory motif mediates heme-dependent degradation of the circadian factor period 2. Mol Cell Biol. 2008;28:4697–4711. http://www.ncbi.nlm.nih.gov/pubmed/18505821
2007
Wroble BN, Finkielstein CV, Sible JC. Wee1 kinase alters cyclin E/Cdk2 and promotes apoptosis during the early embryonic development of Xenopus laevis. BMC Dev Biol. 2007;7:119. http://www.ncbi.nlm.nih.gov/pubmed/17961226
2006
Finkielstein CV, Overduin M, Capelluto DG. Cell migration and signaling specificity is determined by the phosphatidylserine recognition motif of Rac1. J Biol Chem. 2006;281:27317–27326. http://www.ncbi.nlm.nih.gov/pubmed/16861229
2004
Bemis L, Chan DA, Finkielstein CV, et al. Distinct aerobic and hypoxic mechanisms of HIF-alpha regulation by CSN5. Genes Dev. 2004;18:739–744. http://www.ncbi.nlm.nih.gov/pubmed/15082527
Gai D, Li D, Finkielstein CV, et al. Insights into the oligomeric states, conformational changes, and helicase activities of SV40 large tumor antigen. J Biol Chem. 2004;279:38952–38959. http://www.ncbi.nlm.nih.gov/pubmed/15247252
Gai D, Zhao R, Li D, Finkielstein CV, Chen XS. Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen. Cell. 2004;119:47–60. http://www.ncbi.nlm.nih.gov/pubmed/15454080
2002
Capelluto DG, Kutateladze TG, Habas R, Finkielstein CV, He X, Overduin M. The DIX domain targets dishevelled to actin stress fibres and vesicular membranes. Nature. 2002;419:726–729. http://www.ncbi.nlm.nih.gov/pubmed/12384700
Cymeryng CB, Lotito SP, Colonna C, et al. Expression of nitric oxide synthases in rat adrenal zona fasciculata cells. Endocrinology. 2002;143:1235–1242. http://www.ncbi.nlm.nih.gov/pubmed/11897679
Finkielstein CV, Chen LG, Maller JL. A role for G1/S cyclin-dependent protein kinases in the apoptotic response to ionizing radiation. J Biol Chem. 2002;277:38476–38485. http://www.ncbi.nlm.nih.gov/pubmed/12176996
2001
Finkielstein CV, Lewellyn AL, Maller JL. The midblastula transition in Xenopus embryos activates multiple pathways to prevent apoptosis in response to DNA damage. Proc Natl Acad Sci U S A. 2001;98:1006–1011. http://www.ncbi.nlm.nih.gov/pubmed/11158585
Maller JL, Gross SD, Schwab MS, Finkielstein CV, Taieb FE, Qian YW. Cell cycle transitions in early Xenopus development. Novartis Found Symp. 2001;237:58–73; discussion 73–8. http://www.ncbi.nlm.nih.gov/pubmed/11444050
1999
Neuman I, Lisdero C, Finkielstein C, et al. Activation of a thioesterase specific for very-long-chain fatty acids by adrenergic agonists in perfused hearts. Biochim Biophys Acta. 1999;1451:101–108. http://www.ncbi.nlm.nih.gov/pubmed/10446392
1998
Finkielstein C, Maloberti P, Mendez CF, et al. An adrenocorticotropin-regulated phosphoprotein intermediary in steroid synthesis is similar to an acyl-CoA thioesterase enzyme. Eur J Biochem. 1998;256:60–66. http://www.ncbi.nlm.nih.gov/pubmed/9746346
Finkielstein CV, Maloberti P, Mendez CF, Podesta EJ. A novel arachidonic acid-related thioesterase involved in acute steroidogenesis. Endocr Res. 1998;24:363–371. http://www.ncbi.nlm.nih.gov/pubmed/9888508
1997
Mele PG, Dada LA, Paz C, et al. Involvement of arachidonic acid and the lipoxygenase pathway in mediating luteinizing hormone-induced testosterone synthesis in rat Leydig cells. Endocr Res. 1997;23:15–26. http://www.ncbi.nlm.nih.gov/pubmed/9187535
1996
Dada L, Cornejo Maciel F, Neuman I, et al. Cytosolic and mitochondrial proteins as possible targets of cycloheximide effect on adrenal steroidogenesis. Endocr Res. 1996;22:533–539. http://www.ncbi.nlm.nih.gov/pubmed/8969907
Finkielstein C, Cymeryng C, Paz C, et al. Characterization of the cDNA corresponding to a phosphoprotein (p43) intermediary in the action of ACTH. Endocr Res. 1996;22:521–532. http://www.ncbi.nlm.nih.gov/pubmed/8969906
Mele PG, Dada LA, Paz C, et al. Site of action of proteinases in the activation of steroidogenesis in rat adrenal gland. Biochim Biophys Acta. 1996;1310:260–268. http://www.ncbi.nlm.nih.gov/pubmed/8599603
1995
Cymeryng CB, Paz C, Dada L, et al. ACTH-dependent proteolytic activity of a novel phosphoprotein (p43) intermediary in the activation of phospholipase A2 and steroidogenesis. Endocr Res. 1995;21:281–288. http://www.ncbi.nlm.nih.gov/pubmed/7588391
1994
Paz C, Dada LA, Cornejo Maciel MF, et al. Purification of a novel 43-kDa protein (p43) intermediary in the activation of steroidogenesis from rat adrenal gland. Eur J Biochem. 1994;224:709–716. http://www.ncbi.nlm.nih.gov/pubmed/7925388
Principal Investigator
Carla Finkielstein, PhD
Fellow and Associate Professor
Fralin Life Sciences Institute
Steger Hall | Office 263E | MC 0477
1015 Life Science Circle
Blacksburg, VA 24061-0477
Email: finkielc@vt.edu
Office Phone: (540) 231-1159
Lab Phone: (540) 231-5165